Stress- and negative-affect related drinking and drug use (SNAD) is an especially important maladaptive substance use (SU) pattern that results in negative outcomes (e.g. increased academic and interpersonal problems, driving under the influence of alcohol, delinquent activity, and getting involved in regrettable sexual situations) in adolescents and college students. Given the public health risk associated with these outcomes, this project seeks to engage an interdisciplinary team to identify the factors that promote SNAD in college students. Emergent research suggests that two classes of factors - social learning factors and genetic variation in stress and affective reactivity - represent important risks for engagement in SNAD. The goal of the proposed research is to develop and refine interdisciplinary methodologies to examine the interaction of variation in select candidate genes with mood, psychological expectancies, and life stress to enhance our understanding of college students'SNAD. We will simultaneously examine the roles of social learning and genetic vulnerabilities for engaging in drinking or drug use in response to stress- and affect-related triggers in a sample of 700 college students. In view of the relative paucity of research of this kind in minority populations, we will conduct this study at a college campus with a predominantly African American (AA) student body. This project will unite two previously isolated lines of research on SU behavior, social learning and genetics, in order to investigate SNAD at two levels of analysis: the between-person (MACRO) level, i.e., how social learning factors and genes interact with major life stressors to influence average SU, and the within-person (MICRO) level, i.e., how social learning factors and genes interact with daily stressors to influence SU on a day-to-day basis. This study will involve collaborative efforts by an inter-disciplinary team of investigators who conduct research on the psychosocial, genetic, and endocrine bases of behavior related to substance use and dependence. This project is an outgrowth and extension of recently initiated collaborations of the two PIs over the past 2 years and applies the use of robust month-long daily data capture methodologies and DNA collection/genotyping. We will augment these measures with a salivary cortisol measure of hypothalamic- pituitary-adrenal (HPA) axis activity as a biological measure of inter-individual responses to stress. Understanding the contributions of social learning and genetic risk factors to SNAD at both macro and micro levels is important, as it will inform prevention efforts by potentially allowing early identification of individuals at greatest risk for problem SU, including alcohol and drug use disorders. Results may also make it possible to match specific treatments to individuals'vulnerabilities. Alcohol and drug use among college students is an important public health issue. Emerging research suggests that social learning factors interacting with individual genetic variation and with life stress influence the risk of maladaptive substance use behavior. This proposal seeks to develop robust and novel methodologies to use internet-based technologies to capture daily data about college student life events and behavior related to substance use, and to integrate this information with emerging knowledge about natural variation in genes related to stress reactivity.